Efficacy of Long-term Ribavirin in Non-responders With Chronic Hepatitis C and Advanced Fibrosis
Status:
Terminated
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
The rate of sustained virological response to a course of standard antiviral therapy
(peg-interferon plus ribavirin) of patients with chronic hepatitis C infected by genotype 1
with advanced fibrosis (>F2) is rather low. Monotherapy with ribavirin reduces ALT levels and
necroinflammatory liver activity in up to a half of non-responders to standard antiviral
therapy, but without changes in liver fibrosis or viremia. Such a beneficial effect seems to
be mainly due to the immunomodulatory effect of ribavirin. Portal pressure, as measured by
HVPG, lowers in patients with chronic hepatitis C and advanced fibrosis with end-of-treatment
response to peg-interferon plus ribavirin. Portal pressure reduction in this setting relates
to a reduction of the necroinflammatory liver activity, but not with fibrosis amelioration.
We hypothesize that monotherapy with ribavirin reduces portal pressure in hepatitis C
patients with advanced fibrosis by means of its immunomodulatory and anti-inflammatory
effects, and could constitute an alternative to non-responders to standard antiviral
treatment. Portal pressure measurement has become a validated surrogate outcome measure in
chronic liver disease, since decreasing portal pressure has shown consistent improvement in
survival and clinical outcomes, such as complications of portal hypertension. The primary aim
of this study is to investigate whether ribavirin monotherapy slows the progression of
advanced chronic liver disease by hepatitis C as assessed by a reduction in HVPG.